Today, the U.S. Food and Drug Administration (FDA) approved enasidenib (Idhifa) for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) who have a specific genetic mutation. The drug is approved for use with a companion diagnostic, the RealTime IDH2 Assay, which is used to detect specific mutations in the IDH2 gene in patients with AML.

“Enasidenib is a targeted therapy that fills an unmet need for patients with relapsed or refractory AML who have an IDH2 mutation,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence and Acting Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “The use of enasidenib was associated with a complete remission in some patients and a reduction in the need for both red cell and platelet transfusions.”

Enasidenib is an isocitrate dehydrogenase-2 inhibitor that works by blocking several enzymes that promote cell growth. If the IDH2 mutation is detected in blood or bone marrow samples using the RealTime IDH2 Assay, the patient may be eligible for treatment with enasidenib.

Trial Results

The efficacy of enasidenib was studied in a single-arm trial of 199 patients with relapsed or refractory AML who had IDH2 mutations as detected by the RealTime IDH2 Assay. The trial measured the percentage of patients with no evidence of disease and full recovery of blood counts after treatment (complete remission [CR]), as well as patients with no evidence of disease and partial recovery of blood counts after treatment (complete remission with partial hematologic recover [CRh]). With a minimum of 6 months of treatment, 19% of patients experienced CR for a median 8.2 months, and 4% of patients experienced CRh for a median 9.6 months. Of the 157 patients who required transfusions of blood or platelets due to AML at the start of the study, 34% no longer required transfusions after treatment with enasidenib.

Side Effects and Safety

Common side effects of enasidenib include nausea, vomiting, diarrhea, increased levels of bilirubin, and decreased appetite. Women who are pregnant or breastfeeding should not take enasidenib because it may cause harm to a developing fetus or a newborn baby.

The prescribing information for enasidenib includes a boxed warning that an adverse reaction known as differentiation syndrome can occur and can be fatal if not treated. Sign and symptoms of differentiation syndrome may include fever; dyspnea; acute respiratory distress; radiographic pulmonary infiltrates; pleural or pericardial effusions; rapid weight gain; peripheral edema; or hepatic, renal, or multi-organ dysfunction. At first suspicion of symptoms, doctors should treat patients with corticosteroids and monitor patients closely until symptoms go away.